Side effect of lupron

Here at the Network, we often receive emails or calls from women seeking health care information about specific procedures or tests. Something different’s been happening recently, however: we’ve received several messages from women asking the Network to explore the safety of a drug commonly used in fertility treatments: Lupron® (leuprolide acetate). This drug was originally developed for advanced prostate cancer patients, but is now commonly used to treat women with endometriosis and fibroids, and to aid assisted reproduction procedures. Lupron® is a Gonadotropin-Releasing Hormone Analog/Agonist (GnRH); these drugs shut down the pituitary gland, thereby reducing the amount of testosterone produced by men, and estrogen produced by women. For women, this causes the rapid and artificial onset of menopause – potentially with incapacitating and long-lasting effects.

“My own story is that after taking Lupron I now have bone loss, severe bone and joint pain requiring heavy painkillers to get out of bed, chest pain, tachycardia, fibromyalgia and horrible memory loss, hair loss and weight gain. Prior to Lupron I ran and boxed everyday. I was healthy even though endometriosis caused significant pain. It has now been a year since my Lupron treatments and my life is in medical shambles.”

The women contacting the Network relate very similar experiences: they were healthy but — after using Lupron® – they report having lost their health, their jobs, and more. While only a small percentage of women seem to have such a severe reaction, there is no way to predict who will experience these frightening and debilitating side-effects. Nor does there seem to be any interest on the part of either the Food and Drug Administration (FDA) or Lupron®’s manufacturer to further investigate the drug’s safety or adverse events. One woman who wrote to the Network about her experiences asked, “Who is watching out for us?”

The FDA reports that, as long ago as 1999, it had received adverse drug reports about Lupron® from 4,228 women and 2,943 men.1 These side effects included: tingling, itching, headache and migraine, dizziness, severe joint pain, difficulty breathing, chest pain, nausea, depression, emotional instability, dimness of vision, fainting, weakness, amnesia, hypertension, muscular pain, bone pain, nausea/vomiting, asthma, abdominal pain, insomnia, chronic enlargement of the thyroid, liver function abnormality, vision abnormality, and anxiety, and others.2 In 325 of these cases, the women required hospitalization; 25 women died.3 At the time, the FDA said that it did not have enough staff capacity to assess any causal effect in these cases.

Lupron®’s original manufacturer, Takeda-Abbott Pharmaceuticals (TAP) Pharmaceuticals, has stated that the drug’s side effects are temporary and should last no longer than six months after stopping the medication.4 But, surveys conducted by the Endometriosis Research Center (a patient advocacy group) with women who took Lupron® has indicated that over half of the respondents (51.67%) experienced side effects lasting for longer than six months; for almost one-quarter (23%) of the women, side effects lasted longer than five years.5 Other clinical studies have found that almost three-quarters (72%) of women taking Lupron® experience memory difficulties, and that these memory problems can last as long as six months after the study was conducted.6

The company seems to know that something’s not right. In “a report submitted by TAP Pharmaceuticals to the FDA in April 1998, researchers wrote that they were ‘concerned’ because more than one-third of the women they studied who took Lupron® did not ‘demonstrate either partial reversibility’ or ‘a trend toward return’ of bone mass in the six months after they stopped taking the drug. Further, the researchers noted some women lost as much as 7.3 percent of their bone density during treatment — more than twice the amount the drug’s packaging lists in its warnings. The researchers concluded, ‘A more complete assessment of the effects of Lupron on can only be made with longer term follow-up of these patients.’” 7 But the company never invested in that follow-up research, and the FDA hasn’t yet required it to.

Lupron® for Endometriosis and Fibroids

The FDA approved Lupron® to treat both endometriosis and anemia associated with uterine fibroids. Endometriosis is a painful, chronic disease that affects over five million women and girls in the U.S.8 It occurs when tissue lining the uterus is found outside the uterus, usually in the abdominal-pelvic cavity. This misplaced tissue develops into growths or lesions that respond to the menstrual cycle like the uterine lining: each month the tissue builds up, breaks down, and sheds. Unlike menstrual blood, however, the blood and tissue shed from endometrial growths have no way to leave the body. The result is internal bleeding and inflammation that can cause pain, infertility, scar tissue formation, adhesions, and bowel problems.

Uterine fibroids are benign growths on the uterus’ muscular wall that can cause pelvic pain, heavy bleeding, clotting, and pain during sex. Around three-quarters (77%) of all women of reproductive age in the U.S. will develop fibroids, and 25 percent will experience negative symptoms as a result.9 African-American women are about three times more likely to develop fibroids than women of other racial groups.10

The exact cause of these conditions is not yet known (although there may be a link with estrogen production or exposure to the environmental toxin dioxin) and no non-invasive tests exist to provide a definitive diagnosis. Treatment for fibroids has traditionally involved a complete hysterectomy, which is not an option for women who want to get pregnant later. For endometriosis, laparoscopic or abdominal surgery to remove endometrial lesions can produce relief, but may fail if the surgeon is unskilled or the disease is particularly severe. For these reasons, many doctors encourage women with these conditions to use drug therapy to adjust estrogen levels in an effort to shrink fibroids or lesions. Despite the fact thatno drug has been proven to provide lasting relief for either condition, Lupron® has emerged as the most-frequently prescribed medication for women with fibroids and endometriosis.

Lupron® for Infertility Treatment

Lupron® is also widely used as part of Assisted Reproductive Technology (ART) — fertility treatments such as in vitro fertilization (IVF) in which both eggs and sperm are handled. The Centers for Disease Control and Prevention (CDC) notes that more than one percent of all U.S. births result from assisted reproductive technologies.11 (ART does not include treatments in which only sperm is handled, like artificial insemination, or when the woman takes drugs only to stimulate eggs but they are not retrieved.)

Assisted reproductive technology efforts use GnRHs as part of the process of harvesting donor and non-donor eggs. The hormones are injected into the woman’s body to shut down the ovaries; then other drugs are used to stimulate egg production and facilitate multiple egg extraction. (The eggs are fertilized in a lab and then implanted into the woman.) Lupron® is among the most common GnRH analogs used as part of this process. IVF patients report that they are told that the use of GnRHs is an essential step; some have been required to take Lupron® to continue their IVF treatment, despite any objections they may have had.

There have been no prospective or clinical studies on Lupron®’s safety for ART patients and the FDA has not approved Lupron® for use in infertility treatment or assisted reproduction procedures such as IVF. Its use occurs “off label”, an option that allows an FDA-approved drug to be used for medical purposes neither originally specified in the drug’s approval nor described on the drug’s labeling.

I have been to a total of 17 doctors since taking Lupron with many different diagnoses and there doesn’t seem to be an end in sight. I don’t know why we can’t seem to get someone in the medical field to look into the on-going side effects of this drug. There is something definitely wrong with a drug when you go from being perfectly healthy to having all kinds of medical problems and you know that in your heart it started while on Lupron. I do know that I am not alone. I used to think I was but I have personally spoken to people that have taking Lupron and they are experiencing the same problems.

Significant Safety Concerns

Lupron® is an “antineoplastic agent”, meaning that it is a cancer chemotherapy drug. Like all antineoplastics, Lupron® is harmful to both cancerous and non-cancerous cells — particularly to pregnant women and developing fetuses. In addition to the harmful side-effects reported by women using Lupron® for its approved uses, there are concerns about its effects when used as part of assisted reproductive technologies, such as IVF.

The National Institutes of Health (NIH) and the Occupational Safety and Health Administration (OSHA) categorize Lupron® as a “hazardous drug” that health care workers should only handle when wearing protective gowns and gloves.12 They also recommend that health care professionals who intend to conceive or father a child avoid handling Lupron® or other such hazardous drug for three months before conception.13

Abbott’s patient education materials note that the FDA advises women who are, or may become, pregnant not to take Lupron® because of the risks to the developing fetus.14 The drug information describes “major fetal abnormalities” seen in pregnant rabbits after Lupron® was injected at doses 1/1200–1/12 the human pediatric dose.15 The company states that women who are pregnant should not use Lupron®, recommends the use non-hormonal contraception to prevent pregnancy while on Lupron®, and encourages those who think they might be pregnant to contact their health care providers immediately.16 The popular website, Drugs.com, states flatly: “Lupron causes birth defects.”17

Yet, despite these risks, and the fact that women may experience side effects months after discontinuing the drug, Lupron® is prescribed not only for approved uses to treat endometriosis and fibroid, but also for off-label use in assisted reproductive technologies.

My exposure to Lupron began in 1989, and shortly thereafter I began having multiple health problems, and have subsequently amassed a room full of documents, correspondences and medical literature devoted to the risks of Lupron. Since testifying in March 2003 on these risks in Congress (where I nearly puked on the Senate floor), I’ve been hospitalized 33 times, and am now disabled and had to retire from my career as a psychiatric RN. It’s been very difficult, especially these last five years, but at least I’ve finally been able to start my website: www.LupronVictimsHub.com.

If the drug is doing what it should and helping women suffering from fibroids, endometriosis, or infertility, that’s one thing. But what if the drug doesn’t work or was approved based on faulty data? According to at least one activist, the clinical studies filed with the FDA on Lupron®’s effectiveness at reducing endometriosis-related pain were based on small numbers of women who were also allowed to take other pain-killers (including narcotics) at the same time.18 The Endometriosis Research Center’s survey found that almost half of the responding women (48.19%) reported Lupron® to be “intolerable” and “not helpful” for relief of their endometriosis symptoms.19

Even more startling, the Federal Dept. of Health and Human Services’ Office of Research Integrity determined that the lead investigator involved with studies on Lupron®’s use in treating fibroids and endometriosis committed scientific misconduct, and admitted to falsifying or fabricating 80 percen of the data in two published studies on Lupron®.20 The Federal Register noted that the investigator “altered and fabricated information in permanent patient medical records and notes by changing dates, changing and adding text, and fabricating notes for clinic visits that did not occur.” 21 Those studies were retracted.

It is devastating to agree to an FDA-approved drug, under the care of a physician you trust, only to find yourself sicker than you could possibly imagine, in pain, and unable to get treatment or even be believed.

Avoiding Long-Term Harm: The Informed Rx Decision-Making Consortium

Lupron® is a hazardous drug with side-effects that can last for weeks or months after the drug is discontinued, but do the women taking it know that? It’s not clear how much patients are being informed about Lupron®’s risks – certainly some people might decide that the drug’s harmful effects outweigh the potential benefits. In addition, the fact that the drug has not been approved or assessed for use in ART procedures such as IVF may be of particular concern to both patients and egg donors.

One researcher has commented: “GnRH analogs are not like any other medication currently available for treatment of disease. As we continue to learn more about these analogs’ mechanisms of action, it is increasingly apparent that they do not just affect the gonadal hormones, but are powerful modulators of autonomic neural function.”22 Shouldn’t we know more about these drugs — and Lupron® in particular?

It is an enormous problem that no data are being gathered on Lupron®’s long-term effects on women using the drug for endometriosis, fibroids, or ART. We believe that women must receive complete information about Lupron®’s efficacy and effects in order to make a truly informed decision about whether or not to take the drug. To determine Lupron®’s short- and long-term effects, and create conditions under which patients can provide true informed consent, the NWHN believes that several measures are needed.

The FDA has recently received funding for additional oversight activities and NWHN believes that the agency should review the safety and efficacy of Lupron® for both its approved and off-label uses. As part of this process, the FDA must require Abbott Pharmaceuticals to conduct the assessment of Lupron®’s long-term effects on bone density that the company itself has said were needed. To gather up-to-date information on adverse events, a registry should be established to monitor the drug’s effect on women, as well as on any children exposed to Lupron® either before conception or as part of their mother’s IVF. Women who have experienced adverse events are encouraged to report them to the FDA by contacting MedWatch at http://www.fda.gov/medwatch/report/consumer/consumer.htm.

In order to halt this drug from causing damage to even one more woman’s health, a concerted effort of women, physicians, health officials, researchers and media is needed. The decision to raise public awareness so that other women could be spared the physical, emotional and financial burdens Lupron causes would truly be in the interest of women’s health around the country. The people who are considering taking Lupron are the ones who have the right to know that they are risking a lifetime of symptoms that may cost them their jobs, spouses, savings and quality of life.

In addition, the NWHN has initiated a public education and policy campaign to get the word out about the misuse and dangers of Lupron® and other drugs. Along with the Center for Medical Consumers, the Endometriosis Association, and Our Bodies Ourselves, we have formed The Informed Rx Decision-Making Consortium. The Consortium will work to educate women about inappropriate drug use and provide tools to help them make better-informed decisions about prescription drugs — including how to determine what works, what doesn’t, and what cost-effective alternatives exist. For more information about the Consortium and the campaign, visit the NWHN’s website in the coming months (www.nwhn.org).

This article was written by: Susan K. Flinn, MA

Susan K. Flinn is the Editor of the WHA. Lynne Millican, RN, BSN, provided support and significant assistance with this article; the majority of the research cited comes from her work. For more information about Lupron and this issue, or to read many of the articles cited, see Ms. Millican’s excellent website: www.LupronVictimsHub.com

1 Norsigian J, “Concerns about Lupron™ (leuprolide acetate), used in the process of extracting eggs from women (for IVF, research cloning, and potentially for inheritable human modifications), OBOS Health Resource Center, October 2002, accessed 9/5/08 fromhttp://www.ourbodiesourselves.org/book/companion.asp?id=25&compID=67&page=5
2 Norsigian J, “Egg Donation for IVF and Stem Cell Research: Time to Weigh the Risks to Women’s Health,” OBOS Health Resource Center, 2005, accessed 9/5/08 fromhttp://www.ourbodiesourselves.org/book/companion.asp?id=31&compID=97&page=3
3 Norsigian J, “Concerns about Lupron™ (leuprolide acetate), used in the process of extracting eggs from women (for IVF, research cloning, and potentially for inheritable human modifications)”, OBOS Health Resource Center, October 2002. Accessed 9/5/08 fromhttp://www.ourbodiesourselves.org/book/companion.asp?id=25&compID=67&page=5
4 In 2008, Abbott Pharmaceuticals and Takeda Pharmaceutical Company concluded this joint venture; Abbott Pharmaceuticals now manufacturers Lupron (other pharmaceutical companies also manufacture GnRHa drugs).
5 Endometriosis Research Center (ERC), “Use of GnRH Agonists Prior to an Endometriosis Diagnosis,” Delray, FL: ERC, 2003, p. 2.
6 Varney NR, Syrop C, Kobe CS et al, “Neuropsychologic Dysfunction in Women Following Leuprolide Acetate Induction of Hypoestrogenism”, Journal of Assisted Reproduction and Genetics 1993; 10(1):53; and Newton C, Slota D, Yuzpe AA et al, “Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study”, Fertility and Sterility 1996; 65(6):1253, cited in Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insert www.LupronVictimsHub.com.
7 Norsigian J, “Egg Donation for IF and Stem Cell Research: Time to Weigh the Risks to Women’s Health,” OBOS Health Resource Center, 2005, accessed 9/5/08 from http://www.ourbodiesourselves.org/book/companion.asp?id=31&compID=97&page=3. Citing Lazar K, “Wonder drug for men alleged to cause harm in women,” Boston Herald, August 22, 23, 24, 1999.
8 US. Dept of Health and Human Services (HHS), “Women’s Healthcare Forum — Endometriosis,” Rockville, MD: HHS, August 2008. Accessed 9/8/08 fromhttp://www.womenshealthcareforum.com/endometriosis.cfm.
9 National Institute of Child Health and Human Development (NICHD), “Fact Sheet — Uterine Fibroids”, Rockville, MD: NICHD, December 22, 2005. Accessed 9/8/08 from
10 National Institute of Child Health and Human Development (NICHD), “Fact Sheet — Uterine Fibroids”, Rockville, MD: NICHD, December 22, 2005. Accessed 9/8/08 from

11 CDC, “2005 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Report”, MMWR 2008;57(SS-5):1–23. On-line: http://www.cdc.gov/ART/ART2005 visited 9/16/08.
12 Listed as leuprolide acetate. National Institutes for Occupational Safety and Health (NIOSH), NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in the Healthcare Setting. Cincinnati, OH: Centers for Disease Control and Prevention/NIOSH, Sept. 2004, p. 12, 37. See Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insert www.LupronVictimsHub.com.
13 American Society of Health-System Pharmacists, American Hospital Formulary System Revised Guidelines 1999, Bethesda MD: ASHSP, pp. 1030-1. See Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insertwww.LupronVictimsHub.com.
14 Patient Information on Treatment with Lupron Depot 3.75 mg , and Patient Information on Treatment with Lupron Depot 11.25 mg , Lake Forest, IL: TAP Pharmaceuticals, 2001-2004, p. 3 For more on this issue, see Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insert www.LupronVictimsHub.com.
15 Lupron Depot 3.75 mg Package Insert, Lake Forest, IL: TAP Pharmaceuticals, Oct. 2005, p. 8.
16 Lupron Depot 3.75 mg Package Insert, Lake Forest, IL: TAP Pharmaceuticals, Oct. 2005, p. 6; Patient Information on Treatment with Lupron Depot 3.75 mg ; and Patient Information on Treatment with Lupron Depot 11.25 mg , Lake Forest, IL: TAP Pharmaceuticals, 2001-2004, p. 5.
17 http://www.drugs.com/lupron.html (visited 9/5/08)
18 FDA, New Drug Application (NDA) 20-011: Summary Basis of Approval. Lupron 3.75 mg IM for pain management in endometriosis. Approved October 1990. See Millican L, “Cloning: A Risk to Women”, Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: www.LupronVictimsHub.com..
19 Endometriosis Research Center, “Use of GnRH Agonists Prior to an Endometriosis Diagnosis,” Delray, FL: Endometriosis Research Center, 2003, p. 2.
20 “Findings of Scientific Misconduct”, Federal Register 1996; 61(85):19295-6. Online through:http://www.gpoaccess.gov/fr/retrieve.html. Accessed 9/17/08. cited in Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insert www.LupronVictimsHub.com.
21 “Findings of Scientific Misconduct”, Federal Register 1996; 61(85):19295-6. Online through:http://www.gpoaccess.gov/fr/retrieve.html. Accessed 9/17/08. cited in Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insert www.LupronVictimsHub.com.
22 Mathias JR, Clench MH, “Placebo Controlled Study Randomizing Leuprolide Acetate”, Digestive Diseases and Sciences 1995; 40(6):1405, cited in Millican L, “Cloning: A Risk to Women,” Testimony Before the U.S. Senate, Subcommittee on Science, Technology and Space, March 27, 2003. Available online at: insertwww.LupronVictimsHub.com.

Lupron

SIDE EFFECTS

Clinical Trials

In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. This transient increase was occasionally associated with a temporary worsening of signs and symptoms, usually manifested by an increase in bone pain (see WARNINGS). In a few cases a temporary worsening of existing hematuria and urinary tract obstruction occurred during the first week. Temporary weakness and paresthesia of the lower limbs have been reported in a few cases.

Potential exacerbations of signs and symptoms during the first few weeks of treatment is a concern in patients with vertebral metastases and/or urinary obstruction which, if aggravated, may lead to neurological problems or increase the obstruction.

In a comparative trial of LUPRON INJECTION (leuprolide acetate) versus DES, in 5% or more of the patients receiving either drug, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician. Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug related are excluded.

LUPRON
(N=98)
DES
(N=101)
Number of Reports
Cardiovascular System
Congestive heart failure 1 5
ECG changes/ischemia 19 22
High blood pressure 8 5
Murmur 3 8
Peripheral edema 12 30
Phlebitis/thrombosis 2 10
Gastrointestinal System
Anorexia 6 5
Constipation 7 9
Nausea/vomiting 5 17
Endocrine System
*Decreased testicular size 7 11
*Gynecomastia/breast tenderness or pain 7 63
*Hot flashes 55 12
*Impotence 4 12
Hemic and Lymphatic System
Anemia 5 5
Musculoskeletal System
Bone pain 5 2
Myalgia 3 9
Central/Peripheral Nervous System
Dizziness/lightheadedness 5 7
General pain 13 13
Headache 7 4
Insomnia/sleep disorders 7 5
Respiratory System
Dyspnea 2 8
Sinus congestion 5 6
Integumentary System
Dermatitis 5 8
Urogenital System
Frequency/urgency 6 8
Hematuria 6 4
Urinary tract infection 3 7
Miscellaneous
Asthenia 10 10
* Physiologic effect of decreased testosterone.

In this same study, the following adverse reactions were reported in less than 5% of the patients on LUPRON.

Cardiovascular System—Angina, Cardiac arrhythmias, Myocardial infarction, Pulmonary emboli; Gastrointestinal System—Diarrhea, Dysphagia, Gastrointestinal bleeding, Gastrointestinal disturbance, Peptic ulcer, Rectal polyps; Endocrine System—Libido decrease, Thyroid enlargement; Musculoskeletal System—Joint pain; Central/Peripheral Nervous System—Anxiety, Blurred vision, Lethargy, Memory disorder, Mood swings, Nervousness, Numbness, Paresthesia, Peripheral neuropathy, Syncope/blackouts, Taste disorders; Respiratory System—Cough, Pleural rub, Pneumonia, Pulmonary fibrosis; Integumentary System— Carcinoma of skin/ear, Dry skin, Ecchymosis, Hair loss, Itching, Local skin reactions, Pigmentation, Skin lesions; Urogenital System—Bladder spasms, Dysuria, Incontinence, Testicular pain, Urinary obstruction; Miscellaneous—Depression, Diabetes, Fatigue, Fever/chills, Hypoglycemia, Increased BUN, Increased calcium, Increased creatinine, Infection/inflammation, Ophthalmologic disorders, Swelling (temporal bone).

In an additional clinical trial and from long-term observation of both studies, the following additional adverse events (excluding those considered not drug related) were reported for patients receiving LUPRON.

Cardiovascular System—Bradycardia, Carotid bruit, Extrasystole, Palpitations, Perivascular cuffing (eyes), Ruptured aortic aneurysm, Stroke, Tachycardia, Transient ischemic attack; Gastrointestinal System—Flatus, Dryness of mouth and throat, Hepatitis, Hepatomegaly, Occult blood (rectal exam), Rectal fistula/erythema; Endocrine System—Libido increase, Thyroid nodule; Musculoskeletal System—Ankylosing spondylosis, Arthritis, Blurred disc margins, Bone fracture, Muscle stiffness, Muscle tenderness, Pelvic fibrosis, Spasms/cramps; Central/Peripheral Nervous System—Auditory hallucinations/tinnitus, Decreased hearing, Decreased reflexes, Euphoria, Hyperreflexia, Loss of smell, Motor deficiency; Respiratory System—Chest tightness, Decreased breathing sounds, Hemoptysis, Pleuritic chest pain, Pulmonary infiltrate, Rales/rhonchi, Rhinitis, Strep throat, Wheezing/bronchitis; Integumentary System—Boil (pubic), Bruises, Hives, Keratosis, Mole, Shingles, Spiders; Urogenital System— Blisters on penis, Inguinal hernia, Penile swelling, Post void residual, Prostatic pain, Pyuria; Miscellaneous—Abdominal distention, Facial swelling/edema, Feet burning, Flu, Eyelid growth, Hypoproteinemia, Accidental injury, Knee effusion, Mass, Pallid, Sallow, Weakness.

Postmarketing

During postmarketing surveillance which includes other dosage forms and other patient populations, the following adverse events were reported.

Symptoms consistent with an anaphylactoid or asthmatic process have been rarely (incidence rate of about 0.002%) reported. Rash, urticaria, and photosensitivity reactions have also been reported.

Localized reactions including induration and abscess have been reported at the site of injection.

Symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath) have been reported individually and collectively.

Cardiovascular System -Hypotension, Myocardial infarction; Endocrine System -Diabetes; Gastrointestinal System -Hepatic dysfunction; Hemic and Lymphatic System -Decreased WBC; Integumentary System -Hair growth; Central/Peripheral Nervous System -Convulsion, Spinal fracture/paralysis, Hearing disorder; Miscellaneous -Hard nodule in throat, Weight gain, Increased uric acid; Musculoskeletal System -Tenosynovitis-like symptoms; Respiratory System -Respiratory disorders.

Changes in Bone Density: Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with an LH-RH agonist analog. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with leuprolide acetate for at least six months, underwent bone density studies as a result of pain. The leuprolide-treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density.

Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

See other LUPRON DEPOT and LUPRON INJECTION package inserts for other events reported in the same and different patient populations.

Read the entire FDA prescribing information for Lupron (Leuprolide Acetate Injection)

Women fear drug they used to halt puberty led to health problems

The women reported a wide range of symptoms: 30 percent cited severe joint pain, 29 percent, severe body aches; 26 percent, cracking teeth, and 20 percent reported osteoporosis. More than half reported moderate to life-threatening depression. Fifteen percent of the women rated their suicidal thoughts as life-threatening to severe.

Marrs believes a uniting factor explains the diverse and severe range of symptoms. Lupron cuts off a woman’s estrogen, eliminating a key hormone called estradiol that regulates the energy centers of the cell, the mitochondria. She said the missed connection between the hormone and cellular powerhouse will hurt each woman where her body is most vulnerable.

“If your mitochondria break down, your nerves start to break down, if your nerves start to break down, your muscles break down. It’s the cascade of effects,” said Marrs, chief executive of the Nevada-based Lucine Health Sciences research firm.

At 20, Ward says she felt like her health was failing. She had muscle weakness so severe that she could barely lift her arms to wash her hair. Debilitating pain coursed through her body. Doctors puzzled over her blood disorder. She’s been hospitalized after feeling suicidal and depressed.

Last year, at 25, she suffered a seizure that resulted in a cracked vertebra.

“It was the most intense pain I felt in my entire life,” Ward said.

Then came another diagnosis: osteoporosis.

The condition would come as little surprise to anyone familiar with Lupron’s use in adults. Adult women using the drug to induce menopause after uterine disorders are warned on the drug’s adult label not to take an initial course longer than six months to avoid serious bone density loss. They are also encouraged to take hormonal “add-back” drugs to soften the side effects.

A Journal of Clinical Oncology study published in 2005 of men who take Lupron for prostate cancer found that it “significantly increased” the risk of fractures, with prolonged use raising the risk. Yet the impact on kids’ bones is still up for debate.

In interviews, several pediatric endocrinologists pointed to studies showing that kids’ bones do thin while they’re on Lupron, but then they bounce back to normal. One 2009 study by Italian researchers examining 66 girls found that bone density was significantly lower after treatment, but within about 10 years, returned to a level comparable to women who served as study controls. A German study concluded there was no harm to bones, even though seven of 41 women studied, or 17 percent, had osteopenia several years after their treatment ended, according to the Journal of Clinical Endocrinology & Metabolism.

Other studies published in international medical journals reached different conclusions. Researchers in Taiwan found “a possible major side effect” when they studied 11 girls who started Lupron at around age 8 and continued treatment for about 5 years. When the women were about 20, they performed bone scans and found that 45 percent of the women had lower-than-average bone density and merited a diagnosis of osteopenia.

Another study by researchers in Turkey concluded that treatment with Lupron for precocious puberty “may have adverse effect on bone health” due to severe vitamin D deficiencies. Their study, published by the West Indian Medical Journal, found that 13 children on Lupron for precocious puberty had serious vitamin short fallings, compared to two children in a control group.

Canadian researchers also identified five children who developed the same bone problem within years of taking a puberty-delaying drug, according to a 2013 study in Hormone Research in Paediatrics, a medical journal. The children each suffered from slippage in the long bone of the leg, near the hip, due to “a lack of adequate sex hormone exposure at a ‘critical period’ of bone formation.”

The FDA considers the drug’s impact on children’s bones an unanswered question, according to a statement: “The effects of bone density in children whose central precocious puberty is arrested with a GnRH agonist are considered ‘unknown’ as they have not been studied.”

By and large, though, the U.S. doctors who dispense Lupron to children are not in a position to see problems that may emerge a decade later, said E. Kirk Neely, a Stanford professor and pediatric endocrinologist. He noted that studies done in Europe haven’t identified long-term joint dysfunction or depression as problems.

“I’m concerned. There’s a very fundamental problem. We treat these kids, they disappear and we never see them again,” Neely said. “We don’t have good follow up, particularly in the U.S.”

Whether Lupron is causing the women’s’ long-term problems, “the answer is I don’t know.”

This story was published by Kaiser Health News, an editorially independent program of the Henry J. Kaiser Family Foundation and a nonprofit, nonpartisan health policy research and communication organization not affiliated with Kaiser Permanente. You can view the original report on its website. This story was also published by Reveal from The Center for Investigative Reporting, a nonprofit news organization based in the San Francisco Bay Area. Christina Jewett, formerly of Reveal, is now a senior correspondent at Kaiser Health News.

Lupron Side Effects

Generic Name: leuprolide

Medically reviewed by Drugs.com. Last updated on Jan 30, 2019.

  • Overview
  • Side Effects
  • Dosage
  • Interactions
  • Pregnancy
  • Q & A
  • More

Note: This document contains side effect information about leuprolide. Some of the dosage forms listed on this page may not apply to the brand name Lupron.

For the Consumer

Applies to leuprolide: powder for suspension 1 month, powder for suspension 3 month, powder for suspension 4 month, powder for suspension 6 month, solution

Along with its needed effects, leuprolide (the active ingredient contained in Lupron) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking leuprolide:

For adults

Less common

  • Fast or irregular heartbeat

Rare

  • Bone, muscle, or joint pain
  • fainting
  • fast or irregular breathing
  • numbness or tingling of the hands or feet
  • puffiness or swelling of the eyelids or around the eyes
  • skin rash, hives, or itching
  • sudden, severe decrease in blood pressure and collapse
  • tightness in the chest
  • troubled breathing

For males only (adults)

More common

  • Arm, back, or jaw pain
  • bloody or cloudy urine
  • blurred vision
  • chest pain or discomfort
  • difficult, burning, or painful urination
  • difficulty with moving
  • dizziness
  • frequent urge to urinate
  • headache
  • increased urge to urinate during the night
  • muscle pain or stiffness
  • nausea
  • nervousness
  • pain in the joints
  • pale skin
  • pounding in the ears
  • slow or fast heartbeat
  • sweating
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • waking to urinate at night

Rare

  • Pain in the groin or legs (especially in the calves)

Incidence not known

  • Altered mental status
  • cardiovascular collapse
  • double vision
  • visual changes
  • vomiting

For females only (adults)

Rare

  • Anxiety
  • deepening of voice
  • increased hair growth
  • mental depression
  • mood changes

For children

Rare

  • Body pain
  • burning, itching, redness, or swelling at the injection site

For females only (children)—expected in first few weeks

Rare

  • Vaginal bleeding (continuing)
  • white vaginal discharge (continuing)

Some side effects of leuprolide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

For adults

More common

  • Sudden sweating and feelings of warmth (hot flashes)

Less common

  • Bleeding, bruising, burning, itching, pain, redness, or swelling at the injection site
  • decreased interest in sexual intercourse
  • swelling of the feet or lower legs
  • swelling or increased tenderness of the breasts
  • trouble sleeping
  • weight gain

For females only (adults)

More common

  • Light, irregular vaginal bleeding
  • stopping of menstrual periods

Less common

  • Burning, dryness, or itching of the vagina
  • pelvic pain

For males only (adults)

More common

  • Back pain
  • chills
  • constipation
  • cough
  • diarrhea
  • fever
  • general feeling of discomfort or illness
  • loss of appetite
  • pain or discomfort at the injection site
  • redness of the face, neck, arms, and occasionally, upper chest
  • runny nose
  • shivering
  • sore throat
  • unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Less common

  • Decreased size of the testicles
  • inability to have or keep an erection

For Healthcare Professionals

Applies to leuprolide: intramuscular kit, intramuscular powder for injection, intramuscular powder for injection extended release, subcutaneous implant, subcutaneous kit, subcutaneous powder for injection extended release, subcutaneous solution

General

The most commonly reported side effects were general pain, peripheral edema, hot flashes, hair loss, ECG changes, ischemia.

Hypersensitivity

Postmarketing reports: Anaphylactoid reactions

Genitourinary

Very common (10% or more): Vaginal dryness (37%), breast tenderness (up to 14%)

Common (1% to 10%): Urinary frequency/urgency, hematuria, urinary tract infection, ovarian hyperstimulation, testicular soreness/pain, breast soreness/tenderness, testicular atrophy, erectile dysfunction, penile disorder, reduced penis size, vaginal hemorrhage, gynecomastia, breast changes, breast enlargement, decrease in testicular size, impotence

Cardiovascular

Very common (10% or more): ECG changes (19%), ischemia (19%)

Common (1% to 10%): Hypertension, murmur, phlebitis, thrombosis, arrhythmias, angina, myocardial infarction

Endocrine

Very common (10% or more): Hot flashes (up to 91%)

Very rare (less than 0.01%): Pituitary apoplexy

Frequency not reported: Transient increase in serum testosterone concentrations during the first 2 days of therapy, ‘flare’ phenomenon

Psychiatric

Common (1% to 10%): Depression, insomnia/sleep disorder, anxiety, nervousness, decreased libido, increased libido

Nervous system

Common (1% to 10%): Dizziness/lightheadedness, headache

Gastrointestinal

Dermatologic

Very common (10% or more): Hair loss (up to 18%)

Musculoskeletal

Frequency not reported: Backache, muscle atrophy, limb pain

Postmarketing reports: : Spinal fracture/paralysis, tenosynovitis-like symptoms

Hematologic

Common (1% to 10%): Anemia

Postmarketing reports: Decreased WBC

Frequency not reported: Decreased red blood cell count/hematocrit/hemoglobin

Respiratory

Local

Frequency not reported: Erythema, ecchymosis, induration, abscess, pain, swelling, nodules, ulcers, irritation, necrosis at the site of injection

Other

Very common (10% or more): General pain (up to 32.7%), peripheral edema (12.5%), asthenia (10%)

Common (1% to 10%): Tinnitus

Frequency not reported: Disturbance of smell/taste, vertigo

Postmarketing reports: Hearing disorder

Hepatic

Frequency not reported: Hepatitis, hepatomegaly

Postmarketing reports: Hepatic dysfunction

Metabolic

Common (1% to 10%): Anorexia

Frequency not reported: Weight gain/loss

Postmarketing reports: Diabetes

1. “Product Information. Lupron (leuprolide).” TAP Pharmaceuticals Inc, Deerfield, IL.

2. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0

3. Cerner Multum, Inc. “Australian Product Information.” O 0

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer

Leuprolide Injection

Before receiving leuprolide injection,

  • tell your doctor and pharmacist if you are allergic to leuprolide, goserelin (Zoladex), histrelin (Supprelin LA, Vantas), nafarelin (Synarel), triptorelin (Trelstar), any other medications, or any of the ingredients in leuprolide injection. Ask your pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: certain medications for irregular heartbeat such as amiodarone (Cordarone), disopyramide (Norpace), procainamide (Procanbid), quinidine, and sotalol (Betapace, Betapace AF, Sorine); medications for seizures; or oral steroids such as dexamethasone (Decadron, Dexpak), methylprednisolone (Medrol), and prednisone (Sterapred). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have unusual vaginal bleeding. Your doctor may tell you not to use leuprolide injection.
  • tell your doctor if you or anyone in your family has or has ever had osteoporosis (condition where bones are thin and more likely to break); if you have a history of drinking alcohol or using tobacco products for a long period of time; or if you have or have ever had depression, cancer that has spread to the spine (backbone), diabetes, urinary obstruction (blockage that causes difficulty urinating), blood in your urine, a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), heart disease, or a low level of potassium, calcium, or magnesium in your blood.
  • you should know that leuprolide is not to be used in women who are pregnant, can become pregnant, or are breast-feeding. Tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. Your doctor may perform a pregnancy test to be sure that you are not pregnant when you begin receiving leuprolide injection. You will need to use a reliable nonhormonal method of birth control to prevent pregnancy while you are receiving leuprolide injection. Talk to your doctor about the types of birth control that are right for you, and continue to use birth control even though you should not have regular menstrual periods during your treatment. If you think you have become pregnant while receiving leuprolide injection, call your doctor immediately. Leuprolide injection can harm the fetus.
  • plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Leuprolide injection may make your skin sensitive to sunlight.

Generic Name: leuprolide (LOO proe lide)
Brand Names: Eligard, Lupron Depot, Lupron Depot-Ped, Lupron, Lupron Depot-Gyn, Viadur

Medically reviewed by Sophia Entringer, PharmD Last updated on Jan 31, 2019.

  • Overview
  • Side Effects
  • Dosage
  • Interactions
  • Pregnancy
  • Q & A
  • More

What is Lupron?

Lupron (leuprolide) overstimulates the body’s own production of certain hormones, which causes that production to shut down temporarily. Leuprolide reduces the amount of testosterone in men or estrogen in women.

Lupron is used in men to treat the symptoms of prostate cancer. Leuprolide only treats the symptoms of prostate cancer and does not treat the cancer itself.

Lupron Depot is used in women to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids.

Lupron Depot-Ped is used to treat precocious (early-onset) puberty in both male and female children.

Lupron may also be used for purposes not listed in this medication guide.

Important information

Certain brands or strengths of leuprolide are used to treat only men and should not be used in women or children. Always check your medicine to make sure you have received the correct brand and strength. Ask the pharmacist if you have any questions about the medicine you receive at the pharmacy.

Lupron can harm an unborn baby or cause birth defects. Do not use if you are pregnant or breastfeeding.

Your symptoms may become temporarily worse when you first start using Lupron. Tell your doctor if this continues for longer than 2 months.

Call your doctor at once if you have a seizure, or unusual changes in mood or behavior.

Before taking this medicine

You should not use Lupron if you are allergic to leuprolide or similar medicines such as buserelin, goserelin, histrelin, nafarelin, or if you have abnormal vaginal bleeding that has not been checked by a doctor.

Certain brands or strengths of leuprolide are used to treat only men and should not be used in women or children. Always check your medicine to make sure you have received the correct brand and strength.

Leuprolide can cause birth defects. Do not use if you are pregnant or breastfeeding. Tell your doctor right away if you become pregnant during treatment.

To make sure Lupron is safe for you, tell your doctor if you have ever had:

  • depression, mental illness or psychosis;

  • seizures or epilepsy;

  • a brain tumor or blood vessel disorder;

  • heart disease, congestive heart failure, long QT syndrome;

  • diabetes;

  • an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or

  • risk factors for bone loss (personal or family history of osteoporosis, smoking, alcohol use, taking steroid or seizure medicines long term).

Lupron usually causes women to stop ovulating or having menstrual periods. However, you may still be able to get pregnant. Use a barrier form of birth control (condom or diaphragm with spermicide). Hormonal contraception (birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

Call your doctor if your periods continue while you are being treated with Lupron.

It is not known whether leuprolide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using Lupron.

How should I use Lupron?

Lupron Depot injection is injected into a muscle, every 1 to 6 months. You may be shown how to use Lupron injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes. Lupron Depot injection must be administered under the supervision of a physician.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.

Different brands or strengths of leuprolide are used to treat different conditions. It is very important that you receive exactly the brand and strength your doctor has prescribed. Always check your medication to make sure you have received the correct brand and type prescribed by your doctor.

Read and carefully follow any Instructions for Use provided with your medicine. Do not use Lupron if you don’t understand all instructions for proper use. Ask your doctor or pharmacist if you have questions.

Your symptoms may become temporarily worse as your hormones adjust to leuprolide. Keep using the medicine as directed, and tell your doctor if your condition is still worse after 2 months of using this medicine.

Leuprolide can have long lasting effects on your body. You may need frequent medical tests while using this medicine and for a short time after your last dose.

Store Lupron in the original carton at room temperature, away from moisture and heat. Protect from light.

Mixed Lupron Depot injection be used immediately (within 30 minutes) as it does not contain a preservative.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while using Lupron?

Leuprolide can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient’s body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Lupron side effects

Get emergency medical help if you have signs of an allergic reaction to Lupron: (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Call your doctor at once if you have:

  • bone pain, loss of movement in any part of your body;

  • swelling, rapid weight gain;

  • a seizure;

  • unusual changes in mood or behavior (crying spells, anger, feeling irritable);

  • sudden chest pain or discomfort, wheezing, dry cough or hack;

  • painful or difficult urination; or

  • high blood sugar – increased thirst, increased urination, hunger, dry mouth, fruity breath odor.

Rare but serious side effects may occur. Call your doctor if you have:

  • pain or unusual sensations in your back, numbness, weakness, or tingly feeling in your legs or feet;

  • muscle weakness or loss of use, loss of bowel or bladder control;

  • heart attack symptoms – chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating; or

  • signs of a stroke – sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech.

Common Lupron side effects may include:

  • hot flashes, sweating, acne, rash, itching, scaly skin;

  • mood changes;

  • headache, general pain;

  • vaginal swelling, itching, or discharge;

  • breakthrough bleeding;

  • weight gain;

  • decreased testicle size; or

  • redness, pain, swelling, or oozing where the shot was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Lupron?

Leuprolide can cause a serious heart problem, especially if you use certain medicines at the same time, such as antibiotics, antifungal medicine, antidepressants, anti-malaria medicine, asthma inhalers, antipsychotic medicine, cancer medicine, certain HIV/AIDS medicine, heart or blood pressure medicine, or medicine to prevent vomiting. Tell your doctor about all your current medicines and any medicine you start or stop using.

Other drugs may interact with leuprolide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Lupron only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2020 Cerner Multum, Inc. Version: 16.07.

Medical Disclaimer

More about Lupron (leuprolide)

  • Side Effects
  • During Pregnancy
  • Dosage Information
  • Drug Interactions
  • Compare Alternatives
  • Support Group
  • Drug class: gonadotropin releasing hormones

Consumer resources

  • Lupron (Advanced Reading)

Other brands: Eligard, Viadur

Professional resources

  • Leuprolide Acetate (AHFS Monograph)
  • … +1 more

Other Formulations

  • Lupron Depot
  • Lupron Depot-Ped

Related treatment guides

  • Precocious Puberty

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